Cutting Edge: Critical Role of Inducible Costimulator in Germinal Center Reactions

Dong, Chen; Temann, Ulla-Angela; Flavell, Richard A.

doi:10.4049/jimmunol.166.6.3659

Cited by 191 publications

(148 citation statements)

References 12 publications

(12 reference statements)

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“…Production of the T cell cytokines IFN␥, IL-17, IL-4, IL-10, and IL-21 was significantly inhibited, whereas IL-6 production was not inhibited (Figure 2). cells (17,31). To determine whether resistance to arthritis in ICOSL Ϫ/Ϫ mice is associated with a reduction in the percentage of GCs and PCs, we examined spleen cells from PG/DDA-immunized mice at the time point when WT mice were arthritic.…”

Section: Resultsmentioning

confidence: 99%

B Cell–Specific Expression of Inducible Costimulator Ligand Is Necessary for the Induction of Arthritis in Mice

Hamel

Cao

Olalekan

et al. 2013

Arthritis & Rheumatology

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Section: Resultsmentioning

confidence: 99%

B Cell–Specific Expression of Inducible Costimulator Ligand Is Necessary for the Induction of Arthritis in Mice

Hamel

Cao

Olalekan

et al. 2013

Arthritis & Rheumatology

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“…Follicular Th cells express high levels of ICOS and are known to be important in the generation of a mature B cell response (34,35), but their role in autoimmune disease pathogenesis has not been well characterized. Our data suggest that the T FH cell in fact plays a critical role in the generation of autoantibodies as well as disease progression in two different autoimmune disease models.…”

Section: Discussionmentioning

confidence: 99%

B7RP-1 Blockade Ameliorates Autoimmunity through Regulation of Follicular Helper T Cells

Metz

Chung

et al. 2009

The Journal of Immunology

121

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Autoimmune diseases are marked by the presence of class-switched, high-affinity autoantibodies with pathogenic potential. Costimulation plays an important role in the activation of T cells and the development of T cell-dependent B cell responses. ICOS plays an indispensable role in the development of follicular helper T cells (TFH cells), which provide cognate help to germinal center (GC) B cells. We show that the levels of TFH cells and GC B cells in two different models of autoimmunity, the New Zealand Black/New Zealand White (NZB/NZW) F1 mouse model of systemic lupus erythematosus and the collagen-induced arthritis model of rheumatoid arthritis, are dependent on the maintenance of the ICOS/B7RP-1 pathway. Treatment with an anti-B7RP-1 Ab ameliorates disease manifestations and leads to a decrease in TFH cells and GC B cells as well as an overall decrease in the frequency of ICOS+ T cells. Coculture experiments of Ag-primed B cells with CXCR5+ or CXCR5− T cells show that blocking B7RP-1 does not directly impact the production of IgG by B cells. These findings further support the role of ICOS in autoimmunity and suggest that the expansion of the TFH cell pool is an important mechanism by which ICOS regulates Ab production.

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“…ICOS is expressed on both CD4 + and CD8 + activated T lymphocytes [6]. ICOS is essential for T cell-dependent B cell responses [7][8][9] and the GC reactions [10,11]. The mechanism underlying B cell activation by ICOS may, at least partially, function through the CD40/CD40L pathway [12].…”

Section: Light Stimulation Enhances Ig Secretionmentioning

confidence: 99%

LIGHT costimulates CD40 triggering and induces immunoglobulin secretion; a novel key partner in T cell‐dependent B cell terminal differentiation

et al. 2004

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The T cell-dependent differentiation and function of B lymphocytes are tightly regulated by TNF ligands (L) and receptors interactions, such as CD40/CD40L, CD27/CD70 and CD134/ CD314L. The LIGHT/HVEM system [homologous to lymphotoxin, inducible expression, competing for GpD of herpes virus, that binds to the herpes virus entry mediator (HVEM), and is expressed on activated T lymphocytes) focused our attention since HVEM has a large distribution that, in addition to T cells, DC or NK, includes tumor and normal B lymphocytes. HVEM was expressed on memory and naive B cells from peripheral blood or tonsils, but not on germinal center (GC) B cells. Costimulation by CD40L+LIGHT induced LIGHT expression at the B lymphocyte surface by a transcriptional mechanism since we detected de novo expression of LIGHT-specific mRNA. LIGHTexpression was further enhanced by triggering of surface IgM, a stimulus that mimics a normal step of B cell physiology, i.e. specific antigen encounter. Stimulation by LIGHT increased the B cell proliferation induced by CD40L, and induced IgG and IgM (but not IgA) secretion. We conclude that LIGHT costimulation, that mimics the B cell encounter with activated LIGHT-expressing T lymphocytes, enhances both B cell proliferation and Ig production, and thus has a central importance for humoral immunity development.

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Cutting Edge: Critical Role of Inducible Costimulator in Germinal Center Reactions

Cited by 191 publications

References 12 publications

B Cell–Specific Expression of Inducible Costimulator Ligand Is Necessary for the Induction of Arthritis in Mice

B Cell–Specific Expression of Inducible Costimulator Ligand Is Necessary for the Induction of Arthritis in Mice

B7RP-1 Blockade Ameliorates Autoimmunity through Regulation of Follicular Helper T Cells

LIGHT costimulates CD40 triggering and induces immunoglobulin secretion; a novel key partner in T cell‐dependent B cell terminal differentiation

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